December 27, 2012

Drug Substitions Due To Shortages Could Prove Harmful For Cancer Patients

According to research led by St. Jude Children's Research Hospital, there is a connection between higher rates of relapse in pediatric cancer patients and drug shortages.

A national drug shortage was linked to a higher rate of relapse among children, teenagers and young adults with Hodgkin's lymphoma, according to the national study.

Survival from the condition went from 88 to 75 percent in two years after the drug cyclophosphamide was substituted for mechlorethamine for treatment of patients with intermediate or high-risk Hodgkin's lymphoma.

The study was launched before the drug shortages started; the change occurred after a mechlorethamine shortage that began in 2009.

No study patients have died, but those who relapsed received additional intensive therapy that is associated with higher odds for infertility and other health problems.

Researchers wrote in the New England Journal of Medicine (NEJM) about an analysis comparing how patients in each group were faring two years after their cancer diagnoses. The report provides the first evidence of a drug shortage adversely impacting treatment outcomes in specific patients.

Many patients and caregivers have had their medical care complicated by drug shortages, primarily generic injectable drugs like mechlorethamine, in recent years. This drug has been used in cancer treatment since the 1960s. Cyclophosphamide has been used in treatment of both adults and children with Hodgkin's lymphoma. The drug was considered a safe and effective alternative to mechlorethamine, based on other studies.

"This is a devastating example of how drug shortages affect patients and why these shortages must be prevented," Monika Metzger, M.D., an associate member of the St. Jude Department of Oncology and the study's principal investigator, said in a statement. "Our results demonstrate that, for many chemotherapy drugs, there are no adequate substitute drugs available."

Drug shortages have been resolved in the past in a variety of ways, and always before a drug substitution became necessary.

"This puts a face on the problem of drug shortages and shows that the problem is real, not theoretical. This is about a curative therapy that we were unable to administer because the drug we needed was not available," said Michael Link, M.D., the senior author of the new report. "Despite heroic efforts by the drug shortage office of the Food and Drug Administration to solve the shortages of a number of medically necessary drugs, it is clear that patients are still suffering from the unavailability of life-saving drugs. A more systematic solution to the problem is needed."

When researchers assessed the substitution of mechlorethamine for cyclophosphamide, they found that disease-free survival was 88 percent for the 181 patients whose treatment included mechlorethamine. It was just 75 percent for the 40 patients who received cyclophosphamide instead.

"We can think of no credible explanation for this dramatic difference in event-free survival other than the drug substitution," the researchers noted.

They found that patients who received cyclophosphamide had fewer unfavorable symptoms and were more likely to have intermediate risk, rather than high-risk Hodgkin's lymphoma.